The aim of this project is to characterize several different functional T-cell subclasses which can be activated by the group of thymus-independent type 2 (TI-2) antigens. Over the past 2 years our laboratory has developed methods to directly measure the activity of suppressor T cells (Ts), helper T cells (TH) and amplifier T cells (TA) activated by the TI antigens type III pneumococcal polysaccharide (S3) and polyvinylpyrrolidone (PVP). We now plan to use these systems to answer the following questions: (1)\Do TI antigens activate different subsets of T cells than do thymus-dependent (TD) antigens? (2)\What is the mechanism by which these T-cell subsets regulate antibody responses to TI antigens and to TD forms of these same antigens? (3)\How do these T cells determine the quality and quantity of the antibody response? (4)\What are the conditions and cell-cell interactions needed to activate these T-cell subsets? These studies will utilize inbred strains of mice. The various T-cell subsets will be activated with antigen according to previously determined methods and then assayed for activity after transfer to normal or irradiated recipients which will be immunized with the same antigen or with a TD form of antigen. Antibody responses will be measured by a hemolytic plaque (PFC) assay. Functional T-cell subsets will be isolated by using antisera to Lyt and Ia antigens. B cells will be obtained by treating spleen cells with anti-Thy 1.2 and complement. Splenic T cells will be obtained by passing spleen cells over nylon wool or by depleting B cells on anti-immunoglobulin coated plates. Answers to the questions we are asking in these studies are important for filling existing gaps in our basic understanding of how the immune response is regulated. A greater understanding of the types of cells which are activated by particular types of antigens and the mechanisms by which they regulate antibody responses is necessary in order to develop more rational and specific therapeutic approaches for the many diseases in which the immune response may produce injury or regulate the disease.